: A variety of symptoms linked to indoor air pollution, including eye, nose, and throat irritation (as well as reflex nasal congestion, rhinorrhea, and sinus headache) are either mediated (or triggered) by trigeminal chemoreception. The premise that humans exhibit significant inter-individual variation in nasal trigeminal irritant sensitivity is one that has been suggested on both clinical and epidemiologic grounds, but experimentally has been incompletely investigated. The purpose of this series of experiments is to systematically explore the influence of personal factors -including age, gender, and allergic rhinitis status- on nasal irritant sensitivity, using stratified samples of non-asthmatic subjects aged 18-69 years. Operationally, "nasal irritant sensitivity" will include both perceptual acuity (the ability of an individual to detect an irritant gas or vapor) and physiologic reactivity (the tendency of individuals to experience reflex-mediated physiologic changes when exposed to irritants). For perceptual acuity, two distinct experimental systems will be employed: detection thresholds using odorless irritant (CO2), and localization thresholds for an odorous volatile organic compound (VOC). Nasal physiologic reactivity will be studies by examining changes in nasal airway resistance (NAR) after both chemical irritant (low-level chlorine) and pharmacologic (aerosolized histamine) provocation. Finally, biochemical markers of mast cell degranulation (tryphase) and neuro-immune modulation (nerve growth factor) will be assayed in nasal lavage fluid pre- and post chemical provocation in a subset of subjects. Issues of test-retest stability and cross agent generalizability of sensory tests will be examined, as will the degree of correlation between individual perceptual acuity and physiologic reactivity. The overall goals include: 1) to better understand heterogeneity of upper airway symptom reporting in polluted environments; 2) to evaluate the relationship between functional subcomponents of "nasal irritant sensitivity"; 3) to further standardize psychophysical and provocation testing protocols for possible use in clinical and/or epidemiologic settings; and 4) to explore the pathophysiology of the nasal response to irritants, including selected interactions between the sensory and immune systems.